Integrins play central roles in cell adhesion, migration, and tissue formation, and in the regulation of gene expression, cell growth, and the cytoskeleton. We are characterizing mechanisms of integrin signaling and function by (a) comparing components of different types of adhesion complexes and associated cytoskeletal molecules, (b) identifying regulators of the formation of these integrin complexes, (c) characterizing roles of key cytoskeletal molecules, and (d) defining downstream signal transduction systems and changes in gene expression. Effects of expressing specific proteins and domains on cell biological functions are being characterized. A variety of chimeras containing individual cytoskeletal and signal transduction molecules are being tested as mediators of downstream steps in the hierarchies of responses to integrin receptors. Because integrin functions are crucial for normal embryonic development, wound healing, and differentiated tissue function, these studies provide an opportunity to identify new pathways as potential targets for diagnosis and therapy.